Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Abstract

bDue to the increase in multidrug-resistant Enterobacteriaceae, the interest in older antimicrobial agents, like fosfomycin, has increased. In this study, we used agar dilution for testing susceptibilities to fosfomycin in a collection of 107 carbapenem-nonsusceptible Enterobacteriaceae isolates, of which 80 produced various types of carbapenemases, including KPC, VIM, NDM, and OXA-48. Overall, 78% of the strains had fosfomycin MICs of <32 mg/liter and were thus considered to be susceptible according to the current EUCAST breakpoint. The MIC 50 and MIC 90 were 8 mg/liter and 512 mg/liter, respectively. Escherichia coli strains had significantly lower fosfomycin MICs than the Klebsiella pneumoniae and Enterobacter cloacae strains. Furthermore, comparisons of the susceptibility testing methods, like Etest and disk diffusion, were performed against agar dilution as the reference method. Essential agreement between Etest and agar dilution was 78.9%, and categorical agreement between the two methods was 92.5%, with 20% very major errors and 2.6% major errors. Disk diffusion was studied with 50-g and 200-g fosfomycin disks, but no inhibition zone breakpoint that reduced very major and major errors to an acceptable level was found. Etest and disk diffusion showed poor agreement with fosfomycin agar dilution.

Carbapenem- and Colistin-Resistant Enterobacter cloacae from Delta, Colorado, in 2015

“…A majority of extended-spectrum ␤-lactamase (ESBL)-and carbapenemase-producing isolates of Enterobacteriaceae are susceptible to fosfomycin (42), with susceptibility in 47 to 72% E. cloacae isolates (EUCAST criteria) (43,44). This isolate was resistant to fosfomycin, consistent with the chromosomally encoded glutathione transferase (fosA).…”

Neisseria gonorrhoeae and fosfomycin: Past, present and future

“…Because zone of inhibition breakpoints have not been described for fosfomycin and N. gonorrhoeae, testing for clinical use is limited to agar dilution or Etest. Furthermore, concordance between agar dilution and Etest methods has been reportedly low for fosfomycin [36,37]. Whilst maximum urine concentrations >4000 mg/L have been reported following 3 g orally, peak serum concentrations of only 22-32 mg/L were reported within 2 h [30].…”

Complete Sequence of a Novel IncR-F33:A–:B– Plasmid, pKP1034, Harboring fosA3 , bla KPC-2 , bla CTX-M-65 , bla SHV-12 , and rmtB from an Epidemic Klebsiella pneumoniae Sequence Type 11 Strain in China

“…Fosfomycin seems to retain in vitro activity against many carbapenem-resistant Enterobacteriaceae and has been recently reintroduced into the fight against these superbugs, including KPC-KP strains (1)(2)(3)(4). A previous study showed that only 43.4% of KPC-KP strains retained susceptibility to fosfomycin in a Chinese university hospital (5).…”